ID GLI1_HUMAN Reviewed; 1106 AA. AC P08151; D0EUY3; E9PQQ9; F5H6H8; Q8TDN9; DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1988, sequence version 1. DT 02-SEP-2026, entry version 250. DE RecName: Full=Transcription activator GLI1; DE AltName: Full=Glioma-associated oncogene; DE AltName: Full=Oncogene GLI; GN Name=GLI1 {ECO:0000303|PubMed:19706761, ECO:0000312|HGNC:HGNC:4317}; GN Synonyms=GLI; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION. RX PubMed=2832761; DOI=10.1038/332371a0; RA Kinzler K.W., Ruppert J.M., Bigner S.H., Vogelstein B.; RT "The GLI gene is a member of the Kruppel family of zinc finger proteins."; RL Nature 332:371-374(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-933 AND GLN-1100. RA Yoon J.W., Kent P., Clark A., Patterson J., Villavicencio E., RA Iannaccone P., Walterhouse D.; RT "Polymorphic variants of the human oncogene GLI1 function similarly."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING, FUNCTION, RP SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY. RX PubMed=19706761; DOI=10.1158/0008-5472.can-09-0886; RA Lo H.W., Zhu H., Cao X., Aldrich A., Ali-Osman F.; RT "A novel splice variant of GLI1 that promotes glioblastoma cell migration RT and invasion."; RL Cancer Res. 69:6790-6798(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., RA Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND DNA-BINDING. RX PubMed=2105456; DOI=10.1128/mcb.10.2.634-642.1990; RA Kinzler K.W., Vogelstein B.; RT "The GLI gene encodes a nuclear protein which binds specific sequences in RT the human genome."; RL Mol. Cell. Biol. 10:634-642(1990). RN [7] RP FUNCTION. RX PubMed=10075717; DOI=10.1074/jbc.274.12.8143; RA Dai P., Akimaru H., Tanaka Y., Maekawa T., Nakafuku M., Ishii S.; RT "Sonic Hedgehog-induced activation of the Gli1 promoter is mediated by RT GLI3."; RL J. Biol. Chem. 274:8143-8152(1999). RN [8] RP INTERACTION WITH SUFU, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION. RX PubMed=10559945; DOI=10.1038/13031; RA Kogerman P., Grimm T., Kogerman L., Krause D., Unden A.B., Sandstedt B., RA Toftgaard R., Zaphiropoulos P.G.; RT "Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of RT Gli-1."; RL Nat. Cell Biol. 1:312-319(1999). RN [9] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND INTERACTION WITH RP STK36 AND SUFU. RX PubMed=10806483; DOI=10.1038/35010610; RA Murone M., Luoh S.-L., Stone D., Li W., Gurney A., Armanini M., Grey C., RA Rosenthal A., de Sauvage F.J.; RT "Gli regulation by the opposing activities of fused and suppressor of RT fused."; RL Nat. Cell Biol. 2:310-312(2000). RN [10] RP FUNCTION, INTERACTION WITH ZIC1, AND SUBCELLULAR LOCATION. RX PubMed=11238441; DOI=10.1074/jbc.c000773200; RA Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.; RT "Physical and functional interactions between Zic and Gli proteins."; RL J. Biol. Chem. 276:6889-6892(2001). RN [11] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION, AND FUNCTION. RX PubMed=19878745; DOI=10.1016/j.yexcr.2009.10.018; RA Maloverjan A., Piirsoo M., Michelson P., Kogerman P., Osterlund T.; RT "Identification of a novel serine/threonine kinase ULK3 as a positive RT regulator of Hedgehog pathway."; RL Exp. Cell Res. 316:627-637(2010). RN [12] RP ACETYLATION AT LYS-518. RX PubMed=20081843; DOI=10.1038/ncb2013; RA Canettieri G., Di Marcotullio L., Greco A., Coni S., Antonucci L., RA Infante P., Pietrosanti L., De Smaele E., Ferretti E., Miele E., RA Pelloni M., De Simone G., Pedone E.M., Gallinari P., Giorgi A., RA Steinkuhler C., Vitagliano L., Pedone C., Schinin M.E., Screpanti I., RA Gulino A.; RT "Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase interplay RT regulates Hedgehog signalling through Gli acetylation."; RL Nat. Cell Biol. 12:132-142(2010). RN [13] RP DEGRADATION. RX PubMed=21921029; DOI=10.1074/jbc.m111.274993; RA Schrader E.K., Harstad K.G., Holmgren R.A., Matouschek A.; RT "A three-part signal governs differential processing of Gli1 and Gli3 RT proteins by the proteasome."; RL J. Biol. Chem. 286:39051-39058(2011). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=24076122; DOI=10.1016/j.bbrc.2013.09.090; RA Gilder A.S., Chen Y.B., Jackson R.J. III, Jiang J., Maher J.F.; RT "Fem1b promotes ubiquitylation and suppresses transcriptional activity of RT Gli1."; RL Biochem. Biophys. Res. Commun. 440:431-436(2013). RN [15] RP INTERACTION WITH SUFU. RX PubMed=28965847; DOI=10.1016/j.ajhg.2017.08.017; RA De Mori R., Romani M., D'Arrigo S., Zaki M.S., Lorefice E., Tardivo S., RA Biagini T., Stanley V., Musaev D., Fluss J., Micalizzi A., Nuovo S., RA Illi B., Chiapparini L., Di Marcotullio L., Issa M.Y., Anello D., RA Casella A., Ginevrino M., Leggins A.S., Roosing S., Alfonsi R., Rosati J., RA Schot R., Mancini G.M.S., Bertini E., Dobyns W.B., Mazza T., Gleeson J.G., RA Valente E.M.; RT "Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway RT and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects."; RL Am. J. Hum. Genet. 101:552-563(2017). RN [16] RP FUNCTION, INVOLVEMENT IN PAPA8, VARIANTS PAPA8 113-ARG--ALA-1106 DEL; RP 644-GLN--ALA-1106 DEL AND 780-TRP--ALA-1106 DEL, AND CHARACTERIZATION OF RP VARIANT 780-TRP--ALA-1106 DEL. RX PubMed=28973407; DOI=10.1093/hmg/ddx335; RA Palencia-Campos A., Ullah A., Nevado J., Yildirim R., Unal E., Ciorraga M., RA Barruz P., Chico L., Piceci-Sparascio F., Guida V., De Luca A., RA Kayserili H., Ullah I., Burmeister M., Lapunzina P., Ahmad W., RA Morales A.V., Ruiz-Perez V.L.; RT "GLI1 inactivation is associated with developmental phenotypes overlapping RT with Ellis-van Creveld syndrome."; RL Hum. Mol. Genet. 26:4556-4571(2017). RN [17] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1003, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [18] RP ACTIVITY REGULATION, PHOSPHORYLATION AT SER-102; SER-116 AND SER-130, AND RP MUTAGENESIS OF SER-70; SER-86; SER-102; SER-116; SER-130; SER-146 AND RP SER-201. RX PubMed=35831023; DOI=10.26508/lsa.202101353; RA Bardwell A.J., Wu B., Sarin K.Y., Waterman M.L., Atwood S.X., Bardwell L.; RT "ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of RT GLI1."; RL Life. Sci Alliance 5:0-0(2022). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 234-388 IN COMPLEX WITH DNA, AND RP DNA-BINDING. RX PubMed=8378770; DOI=10.1126/science.8378770; RA Pavletich N.P., Pabo C.O.; RT "Crystal structure of a five-finger GLI-DNA complex: new perspectives on RT zinc fingers."; RL Science 261:1701-1707(1993). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 115-131 IN COMPLEX WITH SUFU, RP INTERACTION WITH SUFU, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=24311597; DOI=10.1107/s0907444913028473; RA Cherry A.L., Finta C., Karlstrom M., Jin Q., Schwend T., Astorga-Wells J., RA Zubarev R.A., Del Campo M., Criswell A.R., de Sanctis D., Jovine L., RA Toftgard R.; RT "Structural basis of SUFU-GLI interaction in human Hedgehog signalling RT regulation."; RL Acta Crystallogr. D 69:2563-2579(2013). RN [21] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 112-128 IN COMPLEX WITH SUFU, RP INTERACTION WITH SUFU, AND FUNCTION. RX PubMed=24217340; DOI=10.1038/ncomms3608; RA Zhang Y., Fu L., Qi X., Zhang Z., Xia Y., Jia J., Jiang J., Zhao Y., Wu G.; RT "Structural insight into the mutual recognition and regulation between RT Suppressor of Fused and Gli/Ci."; RL Nat. Commun. 4:2608-2608(2013). RN [22] RP VARIANTS ALA-884; ASP-933 AND GLN-1100. RX PubMed=10951255; DOI=10.1046/j.1523-1747.2000.00065.x; RA Wang X.Q., Chan N., Rothnagel J.A.; RT "Identification of polymorphic variants of the GLI1 oncogene."; RL J. Invest. Dermatol. 115:328-329(2000). RN [23] RP VARIANTS [LARGE SCALE ANALYSIS] ALA-210; ILE-514 AND GLN-817. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [24] RP VARIANT PPD1 GLN-506, AND INVOLVEMENT IN PPD1. RX PubMed=30620395; DOI=10.1111/cge.13495; RA Ullah A., Umair M., Majeed A.I., Abdullah Jan A., Ahmad W.; RT "A novel homozygous sequence variant in GLI1 underlies first case of RT autosomal recessive pre-axial polydactyly."; RL Clin. Genet. 95:540-541(2019). CC -!- FUNCTION: Transcription activator that acts as a key effector of the CC smoothened signaling pathway, and which plays a role in craniofacial CC development and digital development, as well as development of the CC central nervous system and gastrointestinal tract (PubMed:10806483, CC PubMed:11238441, PubMed:19706761, PubMed:19878745, PubMed:24076122, CC PubMed:24217340, PubMed:24311597, PubMed:28973407). Binds to the DNA CC consensus sequence 5'-GACCACCCA-3' (PubMed:2105456, PubMed:24217340, CC PubMed:2832761, PubMed:8378770). Activated in response to smoothened CC signaling: in presence of hedgehog (DHH, IHH or SHH) and subsequent CC activation of smoothened, GLI1 translocates to the nucleus and promotes CC expression of target genes (PubMed:2105456). In contrast to GLI2 and CC GLI3, does not contain a repressor domain and only acts as a CC transcription activator (PubMed:10075717). CC {ECO:0000269|PubMed:10075717, ECO:0000269|PubMed:10806483, CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761, CC ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456, CC ECO:0000269|PubMed:24076122, ECO:0000269|PubMed:24217340, CC ECO:0000269|PubMed:24311597, ECO:0000269|PubMed:2832761, CC ECO:0000269|PubMed:28973407, ECO:0000269|PubMed:8378770}. CC -!- FUNCTION: [Isoform 2]: Acts as a transcriptional activator, but CC activates a different set of genes than isoform 1 (PubMed:19706761). CC Activates expression of CD24, unlike isoform 1 (PubMed:19706761). CC {ECO:0000269|PubMed:19706761}. CC -!- ACTIVITY REGULATION: Maintained in an inactive state by SUFU, which CC sequesters GLI1 in the cytoplasm (PubMed:10806483, PubMed:10559945, CC PubMed:24311597). In presence of hedgehog (DHH, IHH or SHH), smoothened CC is activated, leading to phosphorylation by MAPK1/ERK2 and dissociation CC from SUFU and translocation to the nucleus (PubMed:10806483, CC PubMed:24311597, PubMed:35831023). In absence of hedgehog, smoothened CC is inhibited, promoting degradation of GLI1 (PubMed:21921029). CC {ECO:0000269|PubMed:10559945, ECO:0000269|PubMed:10806483, CC ECO:0000269|PubMed:21921029, ECO:0000269|PubMed:24311597, CC ECO:0000269|PubMed:35831023}. CC -!- SUBUNIT: Interacts with SUFU; sequestering GLI1 in the cytoplasm CC (PubMed:10806483, PubMed:10559945, PubMed:24217340, PubMed:24311597, CC PubMed:28965847). Interacts with KIF7 (By similarity). Interacts with CC STK36 (PubMed:10806483). Interacts with ZIC1; the interaction enhances CC transcription activation (PubMed:11238441). CC {ECO:0000250|UniProtKB:P47806, ECO:0000269|PubMed:10559945, CC ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, CC ECO:0000269|PubMed:24217340, ECO:0000269|PubMed:24311597, CC ECO:0000269|PubMed:28965847}. CC -!- INTERACTION: CC P08151; P29972: AQP1; NbExp=3; IntAct=EBI-308084, EBI-745213; CC P08151; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-308084, EBI-744545; CC P08151; P53673: CRYBA4; NbExp=3; IntAct=EBI-308084, EBI-7519711; CC P08151; Q96CN9: GCC1; NbExp=3; IntAct=EBI-308084, EBI-746252; CC P08151; Q96J02: ITCH; NbExp=4; IntAct=EBI-308084, EBI-1564678; CC P08151; Q13526: PIN1; NbExp=3; IntAct=EBI-308084, EBI-714158; CC P08151; P54646: PRKAA2; NbExp=3; IntAct=EBI-308084, EBI-1383852; CC P08151; P23443: RPS6KB1; NbExp=4; IntAct=EBI-308084, EBI-1775921; CC P08151; P23443-2: RPS6KB1; NbExp=2; IntAct=EBI-308084, EBI-6093204; CC P08151; Q9UMX1: SUFU; NbExp=27; IntAct=EBI-308084, EBI-740595; CC P08151; Q9UMX1-1: SUFU; NbExp=2; IntAct=EBI-308084, EBI-740615; CC P08151; Q9UMX1-2: SUFU; NbExp=4; IntAct=EBI-308084, EBI-740621; CC P08151; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-308084, EBI-5235829; CC P08151; P40337-1: VHL; NbExp=2; IntAct=EBI-308084, EBI-3504450; CC P08151; P40337-3: VHL; NbExp=2; IntAct=EBI-308084, EBI-301270; CC P08151; Q9QZS3-2: Numb; Xeno; NbExp=4; IntAct=EBI-308084, EBI-3896014; CC P08151; P46684: Zic1; Xeno; NbExp=2; IntAct=EBI-308084, EBI-308006; CC P08151-1; P41743: PRKCI; NbExp=3; IntAct=EBI-16038799, EBI-286199; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10806483, CC ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, CC ECO:0000269|PubMed:24076122}. Nucleus {ECO:0000269|PubMed:10806483, CC ECO:0000269|PubMed:11238441, ECO:0000269|PubMed:19706761, CC ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:2105456}. Cell CC projection, cilium {ECO:0000250|UniProtKB:P47806}. Note=Sequestered in CC the cytoplasm by SUFU in absence of smoothened signaling CC (PubMed:10806483, PubMed:10559945). Accumulates in primary cilia CC following smoothened activation (By similarity). It then translocates CC to the nucleus, where is activates transcription of target genes CC (PubMed:10806483, PubMed:24311597, PubMed:35831023). Activation and CC translocation to the nucleus is promoted by interaction with STK36 CC (PubMed:10806483). Phosphorylation by ULK3 may promote nuclear CC localization (PubMed:19878745). Translocation to the nucleus is CC promoted by interaction with ZIC1 (PubMed:11238441). CC {ECO:0000250|UniProtKB:P47806, ECO:0000269|PubMed:10559945, CC ECO:0000269|PubMed:10806483, ECO:0000269|PubMed:11238441, CC ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:24311597, CC ECO:0000269|PubMed:35831023}. CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm CC {ECO:0000269|PubMed:19706761}. Nucleus {ECO:0000269|PubMed:19706761}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P08151-1; Sequence=Displayed; CC Name=2; Synonyms=tGLI1; CC IsoId=P08151-2; Sequence=VSP_042215; CC Name=3; CC IsoId=P08151-3; Sequence=VSP_054829; CC -!- TISSUE SPECIFICITY: Detected in testis (at protein level) CC (PubMed:2105456). Testis, myometrium and fallopian tube. Also expressed CC in the brain with highest expression in the cerebellum, optic nerve and CC olfactory tract (PubMed:19878745). Isoform 1 is detected in brain, CC spleen, pancreas, liver, kidney and placenta; isoform 2 is not CC detectable in these tissues (PubMed:19706761). CC {ECO:0000269|PubMed:19706761, ECO:0000269|PubMed:19878745, CC ECO:0000269|PubMed:2105456}. CC -!- TISSUE SPECIFICITY: [Isoform 2]: Undetectable in normal cells but CC highly expressed in cancer cells. {ECO:0000269|PubMed:19706761}. CC -!- INDUCTION: Isoform 1 and isoform 2 are amplified in glioblastoma cells. CC {ECO:0000269|PubMed:19706761}. CC -!- PTM: Phosphorylated in vitro by ULK3 (PubMed:19878745). Phosphorylation CC by PRKCD inhibits its activity by decreasing its localization to the CC nucleus (By similarity). Phosphorylation at Ser-102, Ser-116 and Ser- CC 130 by MAPK1/ERK2 in response to smoothened activation, promotes GLI1 CC dissociation from SUFU inhibitor and translocation to the nucleus CC (PubMed:35831023). {ECO:0000250|UniProtKB:P47806, CC ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:35831023}. CC -!- PTM: Acetylation at Lys-518 down-regulates transcriptional activity. CC Deacetylated by HDAC1. {ECO:0000269|PubMed:20081843}. CC -!- PTM: Degradaded by the proteasome in absence of smoothened signaling. CC {ECO:0000269|PubMed:21921029}. CC -!- PTM: Ubiquitinated by the CRL2(FEM1B) complex, suppressing GLI1 CC transcriptional activator activity. {ECO:0000269|PubMed:24076122}. CC -!- DISEASE: Polydactyly, postaxial, A8 (PAPA8) [MIM:618123]: A form of CC postaxial polydactyly, a condition characterized by the occurrence of CC supernumerary digits in the upper and/or lower extremities. In CC postaxial polydactyly type A, the extra digit is well-formed and CC articulates with the fifth or a sixth metacarpal/metatarsal. PAPA8 is CC an autosomal recessive condition characterized by the presence of CC postaxial extra digits (hexadactyly) on the hands and/or the feet. CC {ECO:0000269|PubMed:28973407}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Polydactyly, preaxial 1 (PPD1) [MIM:174400]: A form of CC polydactyly, a condition defined by the occurrence of supernumerary CC digits in the upper and/or lower extremities. Preaxial or radial CC polydactyly refers to the presence of extra digits on the radial side CC of the hand. PPD1 is an autosomal recessive form characterized by CC duplication of the distal phalanx of the thumb. CC {ECO:0000269|PubMed:30620395}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the GLI C2H2-type zinc-finger protein family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/310/GLI"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X07384; CAA30297.1; -; mRNA. DR EMBL; AF316573; AAM13391.1; -; Genomic_DNA. DR EMBL; GQ890670; ACX35434.1; -; mRNA. DR EMBL; AC022506; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC013000; AAH13000.1; -; mRNA. DR CCDS; CCDS53806.1; -. [P08151-2] DR CCDS; CCDS53807.1; -. [P08151-3] DR CCDS; CCDS8940.1; -. [P08151-1] DR PIR; S00672; TVHUGL. DR RefSeq; NP_001153517.1; NM_001160045.2. [P08151-3] DR RefSeq; NP_001161081.1; NM_001167609.2. [P08151-2] DR RefSeq; NP_005260.1; NM_005269.3. [P08151-1] DR RefSeq; XP_011536491.1; XM_011538189.3. [P08151-1] DR PDB; 2GLI; X-ray; 2.60 A; A=234-388. DR PDB; 4BLB; X-ray; 2.80 A; E/F/G/H=115-131. DR PDB; 4KMD; X-ray; 1.70 A; B=112-128. DR PDB; 5OM0; X-ray; 3.20 A; A/B=637-645. DR PDB; 7T91; X-ray; 2.05 A; A/B=234-302. DR AlphaFoldDB; P08151; -. DR MDRepo; P08151; -. DR SMR; P08151; -. DR BioGRID; 108997; 133. DR ComplexPortal; CPX-56; GLI1-SUFU complex. DR DIP; DIP-32536N; -. DR ELM; P08151; -. DR FunCoup; P08151; 546. DR IntAct; P08151; 45. DR MINT; P08151; -. DR NDEx; IQUERY-CP-GLI1; 15 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000228682; -. DR BindingDB; P08151; -. DR ChEMBL; CHEMBL5461; -. DR GlyGen; P08151; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; P08151; -. DR PhosphoSitePlus; P08151; -. DR BioMuta; GLI1; -. DR DMDM; 121323; -. DR jPOST; P08151; -. DR MassIVE; P08151; -. DR PaxDb; 9606-ENSP00000228682; -. DR PeptideAtlas; P08151; -. DR ProteomicsDB; 27194; -. DR ProteomicsDB; 52074; -. [P08151-1] DR ProteomicsDB; 52075; -. [P08151-2] DR Antibodypedia; 4004; 906 antibodies from 49 providers. DR DNASU; 2735; -. DR Ensembl; ENST00000228682.7; ENSP00000228682.2; ENSG00000111087.11. [P08151-1] DR Ensembl; ENST00000528467.1; ENSP00000434408.1; ENSG00000111087.11. [P08151-2] DR Ensembl; ENST00000543426.5; ENSP00000437607.1; ENSG00000111087.11. [P08151-3] DR Ensembl; ENST00000546141.5; ENSP00000441006.1; ENSG00000111087.11. [P08151-2] DR GeneID; 2735; -. DR KEGG; hsa:2735; -. DR MANE-Select; ENST00000228682.7; ENSP00000228682.2; NM_005269.3; NP_005260.1. DR UCSC; uc001snx.4; human. [P08151-1] DR AGR; HGNC:4317; -. DR ClinPGx; PA28720; -. DR CTD; 2735; -. DR DisGeNET; 2735; -. DR GeneCards; GLI1; -. DR GeneReviews; GLI1; -. DR HGNC; HGNC:4317; GLI1. DR HPA; ENSG00000111087; Tissue enhanced (cervix). DR MalaCards; GLI1; -. DR MIM; 165220; gene. DR MIM; 174400; phenotype. DR MIM; 618123; phenotype. DR OpenTargets; ENSG00000111087; -. DR Orphanet; 289; Ellis Van Creveld syndrome. DR Orphanet; 93339; Polydactyly of a biphalangeal thumb and/or hallux. DR Orphanet; 93334; Postaxial polydactyly type A. DR Orphanet; 93335; Postaxial polydactyly type B. DR VEuPathDB; HostDB:ENSG00000111087; -. DR eggNOG; KOG1721; Eukaryota. DR GeneTree; ENSGT00940000160235; -. DR HOGENOM; CLU_003666_0_0_1; -. DR InParanoid; P08151; -. DR OMA; ANPSCGH; -. DR OrthoDB; 3214149at2759; -. DR PAN-GO; P08151; 5 GO annotations based on evolutionary models. DR PhylomeDB; P08151; -. DR PathwayCommons; P08151; -. DR Reactome; R-HSA-5610780; Degradation of GLI1 by the proteasome. DR Reactome; R-HSA-5610787; Hedgehog 'off' state. DR Reactome; R-HSA-5632684; Hedgehog 'on' state. DR Reactome; R-HSA-5635851; GLI proteins bind promoters of Hh responsive genes to promote transcription. DR SignaLink; P08151; -. DR SIGNOR; P08151; -. DR Agora; ENSG00000111087; -. DR BioGRID-ORCS; 2735; 32 hits in 1174 CRISPR screens. DR EvolutionaryTrace; P08151; -. DR GeneWiki; GLI1; -. DR GenomeRNAi; 2735; -. DR Pharos; P08151; Tchem. DR PRO; PR:P08151; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P08151; protein. DR Bgee; ENSG00000111087; Expressed in tibial nerve and 129 other cell types or tissues. DR ExpressionAtlas; P08151; baseline and differential. DR GO; GO:0005930; C:axoneme; IEA:Ensembl. DR GO; GO:0036064; C:ciliary basal body; IDA:HPA. DR GO; GO:0097546; C:ciliary base; TAS:Reactome. DR GO; GO:0097542; C:ciliary tip; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:1990788; C:GLI-SUFU complex; IPI:ComplexPortal. DR GO; GO:0097730; C:non-motile cilium; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central. DR GO; GO:0008017; F:microtubule binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0048546; P:digestive tract morphogenesis; TAS:BHF-UCL. DR GO; GO:0009913; P:epidermal cell differentiation; IDA:UniProtKB. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB. DR GO; GO:0001649; P:osteoblast differentiation; IDA:UniProtKB. DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IDA:BHF-UCL. DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; IDA:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB. DR GO; GO:0045740; P:positive regulation of DNA replication; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0030850; P:prostate gland development; IEA:Ensembl. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:ComplexPortal. DR GO; GO:0045667; P:regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0008589; P:regulation of smoothened signaling pathway; TAS:UniProtKB. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0007224; P:smoothened signaling pathway; IDA:UniProtKB. DR GO; GO:0007286; P:spermatid development; IEA:Ensembl. DR FunFam; 3.30.160.60:FF:000019; GLI family zinc finger 3; 1. DR FunFam; 3.30.160.60:FF:000031; GLI family zinc finger 3; 1. DR FunFam; 3.30.160.60:FF:000036; GLI family zinc finger 3; 1. DR FunFam; 3.30.160.60:FF:000048; GLI family zinc finger 3; 1. DR FunFam; 3.30.160.60:FF:000068; GLI family zinc finger 3; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 5. DR IDEAL; IID00774; -. DR InterPro; IPR043359; GLI-like. DR InterPro; IPR056436; Znf-C2H2_ZIC1-5/GLI1-3-like. DR InterPro; IPR036236; Znf_C2H2_sf. DR InterPro; IPR013087; Znf_C2H2_type. DR PANTHER; PTHR45718; TRANSCRIPTIONAL ACTIVATOR CUBITUS INTERRUPTUS; 1. DR PANTHER; PTHR45718:SF2; ZINC FINGER PROTEIN GLI1; 1. DR Pfam; PF00096; zf-C2H2; 2. DR Pfam; PF23561; zf-C2H2_15; 1. DR SMART; SM00355; ZnF_C2H2; 5. DR SUPFAM; SSF57667; beta-beta-alpha zinc fingers; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Cell projection; Cytoplasm; Developmental protein; Differentiation; KW Disease variant; DNA-binding; Isopeptide bond; Metal-binding; Nucleus; KW Phosphoprotein; Proteomics identification; Proto-oncogene; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..1106 FT /note="Transcription activator GLI1" FT /id="PRO_0000047197" FT ZN_FING 235..260 FT /note="C2H2-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 268..295 FT /note="C2H2-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 301..325 FT /note="C2H2-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 331..356 FT /note="C2H2-type 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT ZN_FING 362..387 FT /note="C2H2-type 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042" FT REGION 1..20 FT /note="SNAG domain" FT /evidence="ECO:0000250" FT REGION 120..124 FT /note="Interaction with SUFU" FT /evidence="ECO:0000269|PubMed:24217340, FT ECO:0000269|PubMed:24311597" FT REGION 283..291 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:8378770" FT REGION 345..350 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:8378770" FT REGION 375..485 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 375..381 FT /note="Interaction with DNA" FT /evidence="ECO:0000269|PubMed:8378770" FT REGION 516..580 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 732..792 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 817..889 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 914..942 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1054..1087 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 413..428 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 442..463 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 544..560 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 737..753 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 754..766 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 768..779 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 102 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:35831023" FT MOD_RES 116 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:35831023" FT MOD_RES 130 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:35831023" FT MOD_RES 518 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:20081843" FT CROSSLNK 1003 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..128 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_054829" FT VAR_SEQ 34..74 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:19706761" FT /id="VSP_042215" FT VARIANT 113..1106 FT /note="Missing (in PAPA8)" FT /evidence="ECO:0000269|PubMed:28973407" FT /id="VAR_081480" FT VARIANT 210 FT /note="P -> A (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035557" FT VARIANT 506 FT /note="L -> Q (in PPD1; uncertain significance; FT dbSNP:rs753690500)" FT /evidence="ECO:0000269|PubMed:30620395" FT /id="VAR_082590" FT VARIANT 514 FT /note="T -> I (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035558" FT VARIANT 644..1106 FT /note="Missing (in PAPA8)" FT /evidence="ECO:0000269|PubMed:28973407" FT /id="VAR_081481" FT VARIANT 780..1106 FT /note="Missing (in PAPA8; decreased transcriptional FT activity; reduced expression of the GLI1 target PTCH1 FT observed in patient fibroblasts after chemical induction of FT the hedgehog pathway)" FT /evidence="ECO:0000269|PubMed:28973407" FT /id="VAR_081482" FT VARIANT 817 FT /note="E -> Q (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035559" FT VARIANT 884 FT /note="D -> A" FT /evidence="ECO:0000269|PubMed:10951255" FT /id="VAR_015114" FT VARIANT 933 FT /note="G -> D (in dbSNP:rs2228224)" FT /evidence="ECO:0000269|PubMed:10951255, ECO:0000269|Ref.2" FT /id="VAR_015115" FT VARIANT 1012 FT /note="G -> V (in dbSNP:rs2229300)" FT /id="VAR_052723" FT VARIANT 1100 FT /note="E -> Q (in dbSNP:rs2228226)" FT /evidence="ECO:0000269|PubMed:10951255, ECO:0000269|Ref.2" FT /id="VAR_015116" FT MUTAGEN 70 FT /note="S->A: In 7A mutant; abolished phosphorylation by FT MAPK1/ERK2, preventing dissociation from SUFU; when FT associated with A-86, A-102- A-116, A-130, A-146 and FT A-201." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 86 FT /note="S->A: In 7A mutant; abolished phosphorylation by FT MAPK1/ERK2, preventing dissociation from SUFU; when FT associated with A-70, A-102- A-116, A-130, A-146 and FT A-201." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 102 FT /note="S->A: In 7A mutant; abolished phosphorylation by FT MAPK1/ERK2, preventing dissociation from SUFU; when FT associated with A-70, A-86, A-116, A-130, A-146 and A-201." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 102 FT /note="S->E: Mimics phosphorylation; promotes dissociation FT from SUFU; when associated with E-116 and E-130." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 116 FT /note="S->A: In 7A mutant; abolished phosphorylation by FT MAPK1/ERK2, preventing dissociation from SUFU; when FT associated with A-70, A-86, A-102- A-130, A-146 and A-201." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 116 FT /note="S->E: Mimics phosphorylation; promotes dissociation FT from SUFU; when associated with E-102 and E-130." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 130 FT /note="S->A: In 7A mutant; abolished phosphorylation by FT MAPK1/ERK2, preventing dissociation from SUFU; when FT associated with A-70, A-86, A-102- A-116, A-146 and A-201." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 130 FT /note="S->E: Mimics phosphorylation; promotes dissociation FT from SUFU; when associated with E-102 and E-116." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 146 FT /note="S->A: In 7A mutant; abolished phosphorylation by FT MAPK1/ERK2, preventing dissociation from SUFU; when FT associated with A-70, A-86, A-102- A-116, A-130 and A-201." FT /evidence="ECO:0000269|PubMed:35831023" FT MUTAGEN 201 FT /note="S->A: In 7A mutant; abolished phosphorylation by FT MAPK1/ERK2, preventing dissociation from SUFU; when FT associated with A-70, A-86, A-102- A-116, A-130 and A-146." FT /evidence="ECO:0000269|PubMed:35831023" FT CONFLICT 1106 FT /note="A -> AS (in Ref. 3; ACX35434)" FT /evidence="ECO:0000305" FT STRAND 120..123 FT /evidence="ECO:0007829|PDB:4KMD" FT HELIX 249..255 FT /evidence="ECO:0007829|PDB:7T91" FT HELIX 256..261 FT /evidence="ECO:0007829|PDB:7T91" FT TURN 276..279 FT /evidence="ECO:0007829|PDB:7T91" FT STRAND 282..284 FT /evidence="ECO:0007829|PDB:7T91" FT HELIX 285..296 FT /evidence="ECO:0007829|PDB:7T91" FT HELIX 315..324 FT /evidence="ECO:0007829|PDB:2GLI" FT TURN 325..327 FT /evidence="ECO:0007829|PDB:2GLI" FT STRAND 341..346 FT /evidence="ECO:0007829|PDB:2GLI" FT HELIX 349..354 FT /evidence="ECO:0007829|PDB:2GLI" FT TURN 367..369 FT /evidence="ECO:0007829|PDB:2GLI" FT STRAND 372..375 FT /evidence="ECO:0007829|PDB:2GLI" FT HELIX 376..385 FT /evidence="ECO:0007829|PDB:2GLI" FT HELIX 641..643 FT /evidence="ECO:0007829|PDB:5OM0" SQ SEQUENCE 1106 AA; 117904 MW; E29B11D1A6CD3D91 CRC64; MFNSMTPPPI SSYGEPCCLR PLPSQGAPSV GTEGLSGPPF CHQANLMSGP HSYGPARETN SCTEGPLFSS PRSAVKLTKK RALSISPLSD ASLDLQTVIR TSPSSLVAFI NSRCTSPGGS YGHLSIGTMS PSLGFPAQMN HQKGPSPSFG VQPCGPHDSA RGGMIPHPQS RGPFPTCQLK SELDMLVGKC REEPLEGDMS SPNSTGIQDP LLGMLDGRED LEREEKREPE SVYETDCRWD GCSQEFDSQE QLVHHINSEH IHGERKEFVC HWGGCSRELR PFKAQYMLVV HMRRHTGEKP HKCTFEGCRK SYSRLENLKT HLRSHTGEKP YMCEHEGCSK AFSNASDRAK HQNRTHSNEK PYVCKLPGCT KRYTDPSSLR KHVKTVHGPD AHVTKRHRGD GPLPRAPSIS TVEPKREREG GPIREESRLT VPEGAMKPQP SPGAQSSCSS DHSPAGSAAN TDSGVEMTGN AGGSTEDLSS LDEGPCIAGT GLSTLRRLEN LRLDQLHQLR PIGTRGLKLP SLSHTGTTVS RRVGPPVSLE RRSSSSSSIS SAYTVSRRSS LASPFPPGSP PENGASSLPG LMPAQHYLLR ARYASARGGG TSPTAASSLD RIGGLPMPPW RSRAEYPGYN PNAGVTRRAS DPAQAADRPA PARVQRFKSL GCVHTPPTVA GGGQNFDPYL PTSVYSPQPP SITENAAMDA RGLQEEPEVG TSMVGSGLNP YMDFPPTDTL GYGGPEGAAA EPYGARGPGS LPLGPGPPTN YGPNPCPQQA SYPDPTQETW GEFPSHSGLY PGPKALGGTY SQCPRLEHYG QVQVKPEQGC PVGSDSTGLA PCLNAHPSEG PPHPQPLFSH YPQPSPPQYL QSGPYTQPPP DYLPSEPRPC LDFDSPTHST GQLKAQLVCN YVQSQQELLW EGGGREDAPA QEPSYQSPKF LGGSQVSPSR AKAPVNTYGP GFGPNLPNHK SGSYPTPSPC HENFVVGANR ASHRAAAPPR LLPPLPTCYG PLKVGGTNPS CGHPEVGRLG GGPALYPPPE GQVCNPLDSL DLDNTQLDFV AILDEPQGLS PPPSHDQRGS SGHTPPPSGP PNMAVGNMSV LLRSLPGETE FLNSSA //